This invention relates to clinically useful medicaments having a serotonin antagonism, in particular for treating, ameliorating, andpreventing spastic paralysis or central muscle relaxants for ameliorating myotonia.
Myotonia, which seriously restrains daily life, is induced by any of a number of factors or a combination thereof, for example, cervico-omo-brachial syndromes accompanying stiffness or pain in the neck, shoulder, arm, lumbar, and dorsal skeletal muscles due to abnormal posture, fatigue, changes in the backbone with ageing, etc., shoulder periarthritis accompanying inflammation in the tissues constituting the shoulder joint due to changes in the shoulder joint caused by trauma, etc., and spastic paralysis wherein accelerated limb muscle tonus hinders voluntary movements.
In particular, spastic paralysis is a disease which accompanies limb muscle tonus, stiffening, walking difficulty, etc., and thus seriously restrains daily life.
It has been a practice to treat these diseases mainly with the use of medicaments. At the present stage, central muscle relaxants or peripheral muscle relaxants are administered to patients with these diseases. Particular examples of such central muscle relaxants include Tolperisone hydrochloride, Baclofen, Tizanidine hydrochloride, Chlorzoxazone, and Diazepam. Particular examples of such peripheral muscle relaxants include suxamethonium chloride, Pancuronium bromide, and dantrolene sodium.
Central muscle relaxants act selectively on the central nervous system so as to relaxmuscles. Therefore, it is expected that those action on the upper center would exhibit a more potent muscle relaxant effect. However, there arise at the same time some problems including extrapyramidal symptoms and neurologic manifestations such as sleepiness, sluggishness, and atony. No medicament capable of achieving well-balanced principal action and side effects has been known hitherto.
Diazepam, which is inherently a minor tranquilizer, is efficacious against diseases accompanying mental symptoms such as anxiety, tension and depression. However, its effect is too potent to merely ameliorate myotonia. With the use of diazepam, therefore, spastic paralysis can be relieved but there arise some problems such as dizziness. Suxamethonium chloride and Pancuronium bromide, which are peripheral muscle relaxants, are marketed exclusively as injections, which makes the chronic administration thereof difficult. Dantrolene sodium is processed into injections and preparations for oral use and has a relatively potent muscle relaxant effect. However, it has only a lowmarginof safetyand frequently induces muscular atony. Accordingly, it is difficult for those other than medical specialists to administer this medicine.